Redox modulation of p53: Mechanisms and functional significance

Molecular Carcinogenesis

Volumn 50, Issue 4, 2011, Pages 222-234

  Kim, Do Hee ^a   Kundu, Joydeb Kumar ^a   Surh, Young Joon ^a,b  

^a Seoul National University   (South Korea)

^b Seoul National University   (South Korea)

Author keywords

P53; Redox modulation; Redox status; Thiol modification

Indexed keywords

ANTIOXIDANT; CARCINOGEN; GLUTATHIONE; METAL ION; PROSTAGLANDIN; PROTEIN P53; REDOX EFFECTOR FACTOR 1; THIOREDOXIN REDUCTASE;

ARTICLE; CARCINOGENESIS; CELL FUNCTION; CHEMOPROPHYLAXIS; HUMAN; HYPOXIA; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN STRUCTURE;

APOPTOSIS; CELL CYCLE; DNA REPAIR; GENE EXPRESSION REGULATION; HUMANS; MODELS, BIOLOGICAL; OXIDATION-REDUCTION; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; TUMOR SUPPRESSOR PROTEIN P53;

EID: 79953315362     PISSN: 08991987     EISSN: 10982744     Source Type: Journal    
DOI: 10.1002/mc.20709     Document Type: Article

References (146)

1. Giaccia AJ, Kastan MB. The complexity of p53 modulation: Emerging patterns from divergent signals. Genes Dev 1998; 12: 2973-2983.
2. Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323-331.
3. Baker SJ, Fearon ER, Nigro JM, et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 1989; 244: 217-221.
4. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature 1989; 342: 705-708.
5. ARF, and p300/CBP during the cell cycle and after exposure to ultraviolet irradiation. Cancer Res 2000; 60: 896-900.
6. 2-terminal kinase phosphorylation of p53 on Thr-81 is important for p53 stabilization and transcriptional activities in response to stress. Mol Cell Biol 2001; 21: 2743-2754.
7. Haneda M, Kojima E, Nishikimi A, Hasegawa T, Nakashima I, Isobe K. Protein phosphatase 1, but not protein phosphatase 2A, dephosphorylates DNA-damaging stress-induced phospho-serine 15 of p53. FEBS Lett 2004; 567: 171-174.
8. Higashimoto Y, Saito S, Tong XH, et al. Human p53 is phosphorylated on serines 6 and 9 in response to DNA damage-inducing agents. J Biol Chem 2000; 275: 23199-23203.
9. Kao CF, Chen SY, Chen JY, Wu Lee YH. Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein. Oncogene 2004; 23: 2472-2483.
10. Pearson M, Carbone R, Sebastiani C, et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 2000; 406: 207-210.
11. Fuchs SY, Adler V, Buschmann T, Wu X, Ronai Z. Mdm2 association with p53 targets its ubiquitination. Oncogene 1998; 17: 2543-2547.
12. Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W. Mono- versus polyubiquitination: Differential control of p53 fate by Mdm2. Science 2003; 302: 1972-1975.
13. Xirodimas DP, Saville MK, Bourdon JC, Hay RT, Lane DP. Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 2004; 118: 83-97.
14. Gostissa M, Hengstermann A, Fogal V, et al. Activation of p53 by conjugation to the ubiquitin-like protein SUMO-1. EMBO J 1999; 18: 6462-6471.
15. Rodriguez MS, Desterro JM, Lain S, Midgley CA, Lane DP, Hay RT. SUMO-1 modification activates the transcriptional response of p53. EMBO J 1999; 18: 6455-6461.
16. Arrigo AP. Gene expression and the thiol redox state. Free Radic Biol Med 1999; 27: 936-944.
17. Powis G, Briehl M, Oblong J. Redox signalling and the control of cell growth and death. Pharmacol Ther 1995; 68: 149-173.
18. 2 as a potential endogenous regulator of redox-sensitive transcription factors. Biochem Pharmacol 2006; 72: 1516-1528.
19. Na HK, Surh YJ. Transcriptional regulation via cysteine thiol modification: A novel molecular strategy for chemoprevention and cytoprotection. Mol Carcinog 2006; 45: 368-380.
20. Sun Y, Oberley LW. Redox regulation of transcriptional activators. Free Radic Biol Med 1996; 21: 335-348.
21. Stommel JM, Marchenko ND, Jimenez GS, Moll UM, Hope TJ, Wahl GM. A leucine-rich nuclear export signal in the p53 tetramerization domain: Regulation of subcellular localization and p53 activity by NES masking. EMBO J 1999; 18: 1660-1672.
22. Chen J, Lin J, Levine AJ. Regulation of transcription functions of the p53 tumor suppressor by the mdm-2 oncogene. Mol Med 1995; 1: 142-152.
23. Farmer G, Bargonetti J, Zhu H, Friedman P, Prywes R, Prives C. Wild-type p53 activates transcription in vitro. Nature 1992; 358: 83-86.
24. Fields S, Jang SK. Presence of a potent transcription activating sequence in the p53 protein. Science 1990; 249: 1046-1049.
25. Bargonetti J, Manfredi JJ, Chen X, Marshak DR, Prives C. A proteolytic fragment from the central region of p53 has marked sequence-specific DNA-binding activity when generated from wild-type but not from oncogenic mutant p53 protein. Genes Dev 1993; 7: 2565-2574.
26. Pavletich NP, Chambers KA, Pabo CO. The DNA-binding domain of p53 contains the four conserved regions and the major mutation hot spots. Genes Dev 1993; 7: 2556-2564.
27. Wang Y, Reed M, Wang P, et al. p53 domains: Identification and characterization of two autonomous DNA-binding regions. Genes Dev 1993; 7: 2575-2586.
28. 2 terminus of p53 facilitates transactivation. Cancer Res 1995; 55: 2410-2417.
29. Hainaut P, Milner J. Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res 1993; 53: 4469-4473.
30. Wu HH, Sherman M, Yuan YC, Momand J. Direct redox modulation of p53 protein: Potential sources of redox control and potential outcomes. Gene Ther Mol Biol 1999; 4: 119-132.
31. Rainwater R, Parks D, Anderson ME, Tegtmeyer P, Mann K. Role of cysteine residues in regulation of p53 function. Mol Cell Biol 1995; 15: 3892-3903.
32. Buzek J, Latonen L, Kurki S, Peltonen K, Laiho M. Redox state of tumor suppressor p53 regulates its sequence-specific DNA binding in DNA-damaged cells by cysteine 277. Nucleic Acids Res 2002; 30: 2340-2348.
33. Berlett BS, Stadtman ER. Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 1997; 272: 20313-20316.
34. Dean RT, Fu S, Stocker R, Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 1997; 324: 1-18.
35. Ghezzi P, Bonetto V. Redox proteomics: Identification of oxidatively modified proteins. Proteomics 2003; 3: 1145-1153.
36. Giles GI, Jacob C. Reactive sulfur species: An emerging concept in oxidative stress. Biol Chem 2002; 383: 375-388.
37. Giles NM, Giles GI, Jacob C. Multiple roles of cysteine in biocatalysis. Biochem Biophys Res Commun 2003; 300: 1-4.
38. Parks D, Bolinger R, Mann K. Redox state regulates binding of p53 to sequence-specific DNA, but not to non-specific or mismatched DNA. Nucleic Acids Res 1997; 25: 1289-1295.
39. Cobbs CS, Samanta M, Harkins LE, Gillespie GY, Merrick BA, MacMillan-Crow LA. Evidence for peroxynitrite-mediated modifications to p53 in human gliomas: Possible functional consequences. Arch Biochem Biophys 2001; 394: 167-172.
40. Satoh T, Lipton SA. Redox regulation of neuronal survival mediated by electrophilic compounds. Trends Neurosci 2007; 30: 37-45.
41. Uchida K. Role of reactive aldehyde in cardiovascular diseases. Free Radic Biol Med 2000; 28: 1685-1696.
42. Uchida K, Stadtman ER. Covalent attachment of 4-hydroxynonenal to glyceraldehyde-3-phosphate dehydrogenase. A possible involvement of intra- and intermolecular cross-linking reaction. J Biol Chem 1993; 268: 6388-6393.
43. Sun XZ, Vinci C, Makmura L, et al. Formation of disulfide bond in p53 correlates with inhibition of DNA binding and tetramerization. Antioxid Redox Signal 2003; 5: 655-665.
44. Liu B, Chen Y, St Clair DK. ROS and p53: A versatile partnership. Free Radic Biol Med 2008; 44: 1529-1535.
45. Kosower NS, Kosower EM. The glutathione status of cells. Int Rev Cytol 1978; 54: 109-160.
46. Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother 2003; 57: 145-155.
47. Russo T, Zambrano N, Esposito F, et al. A p53-independent pathway for activation of WAF1/CIP1 expression following oxidative stress. J Biol Chem 1995; 270: 29386-29391.
48. Klatt P, Lamas S. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 2000; 267: 4928-4944.
49. Velu CS, Niture SK, Doneanu CE, Pattabiraman N, Srivenugopal KS. Human p53 is inhibited by glutathionylation of cysteines present in the proximal DNA-binding domain during oxidative stress. Biochemistry 2007; 46: 7765-7780.
50. Arner ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000; 267: 6102-6109.
51. Powis G, Montfort WR. Properties and biological activities of thioredoxins. Annu Rev Biophys Biomol Struct 2001; 30: 421-455.
52. Fernando MR, Nanri H, Yoshitake S, Nagata-Kuno K, Minakami S. Thioredoxin regenerates proteins inactivated by oxidative stress in endothelial cells. Eur J Biochem 1992; 209: 917-922.
53. Ravi D, Muniyappa H, Das KC. Endogenous thioredoxin is required for redox cycling of anthracyclines and p53-dependent apoptosis in cancer cells. J Biol Chem 2005; 280: 40084-40096.
54. Pearson GD, Merrill GF. Deletion of the Saccharomyces cerevisiae TRR1 gene encoding thioredoxin reductase inhibits p53-dependent reporter gene expression. J Biol Chem 1998; 273: 5431-5434.
55. Moos PJ, Edes K, Cassidy P, Massuda E, Fitzpatrick FA. Electrophilic prostaglandins and lipid aldehydes repress redox-sensitive transcription factors p53 and hypoxia-inducible factor by impairing the selenoprotein thioredoxin reductase. J Biol Chem 2003; 278: 745-750.
56. Cassidy PB, Edes K, Nelson CC, Parsawar K, Fitzpatrick FA, Moos PJ. Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles. Carcinogenesis 2006; 27: 2538-2549.
57. Seemann S, Hainaut P. Roles of thioredoxin reductase 1 and APE/Ref-1 in the control of basal p53 stability and activity. Oncogene 2005; 24: 3853-3863.
58. Xanthoudakis S, Miao GG, Curran T. The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. Proc Natl Acad Sci USA 1994; 91: 23-27.
59. Xanthoudakis S, Curran T. Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity. EMBO J 1992; 11: 653-665.
60. Xanthoudakis S, Miao G, Wang F, Pan YC, Curran T. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J 1992; 11: 3323-3335.
61. Walker LJ, Craig RB, Harris AL, Hickson ID. A role for the human DNA repair enzyme HAP1 in cellular protection against DNA damaging agents and hypoxic stress. Nucleic Acids Res 1994; 22: 4884-4889.
62. Yao KS, Xanthoudakis S, Curran T, O'Dwyer PJ. Activation of AP-1 and of a nuclear redox factor, Ref-1, in the response of HT29 colon cancer cells to hypoxia. Mol Cell Biol 1994; 14: 5997-6003.
63. Jayaraman L, Murthy KG, Zhu C, Curran T, Xanthoudakis S, Prives C. Identification of redox/repair protein Ref-1 as a potent activator of p53. Genes Dev 1997; 11: 558-570.
64. Hupp TR, Meek DW, Midgley CA, Lane DP. Regulation of the specific DNA binding function of p53. Cell 1992; 71: 875-886.
65. Hupp TR, Meek DW, Midgley CA, Lane DP. Activation of the cryptic DNA binding function of mutant forms of p53. Nucleic Acids Res 1993; 21: 3167-3174.
66. Meira LB, Cheo DL, Hammer RE, Burns DK, Reis A, Friedberg EC. Genetic interaction between HAP1/REF-1 and p53. Nat Genet 1997; 17: 145.
67. Seo YR, Kelley MR, Smith ML. Selenomethionine regulation of p53 by a ref1-dependent redox mechanism. Proc Natl Acad Sci USA 2002; 99: 14548-14553.
68. Hainaut P, Rolley N, Davies M, Milner J. Modulation by copper of p53 conformation and sequence-specific DNA binding: Role for Cu(II)/Cu(I) redox mechanism. Oncogene 1995; 10: 27-32.
69. Verhaegh GW, Richard MJ, Hainaut P. Regulation of p53 by metal ions and by antioxidants: Dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper. Mol Cell Biol 1997; 17: 5699-5706.
70. Wu HH, Momand J. Pyrrolidine dithiocarbamate prevents p53 activation and promotes p53 cysteine residue oxidation. J Biol Chem 1998; 273: 18898-18905.
71. Wu HH, Thomas JA, Momand J. p53 protein oxidation in cultured cells in response to pyrrolidine dithiocarbamate: A novel method for relating the amount of p53 oxidation in vivo to the regulation of p53-responsive genes. Biochem J 2000; 351: 87-93.
72. Furuta S, Ortiz F, Zhu Sun X, Wu HH, Mason A, Momand J. Copper uptake is required for pyrrolidine dithiocarbamate-mediated oxidation and protein level increase of p53 in cells. Biochem J 2002; 365: 639-648.
73. Verhaegh GW, Parat MO, Richard MJ, Hainaut P. Modulation of p53 protein conformation and DNA-binding activity by intracellular chelation of zinc. Mol Carcinog 1998; 21: 205-214.
74. Fojta M, Kubicarova T, Vojtesek B, Palecek E. Effect of p53 protein redox states on binding to supercoiled and linear DNA. J Biol Chem 1999; 274: 25749-25755.
75. Meplan C, Richard MJ, Hainaut P. Metalloregulation of the tumor suppressor protein p53: Zinc mediates the renaturation of p53 after exposure to metal chelators in vitro and in intact cells. Oncogene 2000; 19: 5227-5236.
76. Hofmann TG, Moller A, Sirma H, et al. Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol 2002; 4: 1-10.
77. Puca R, Nardinocchi L, Gal H, et al. Reversible dysfunction of wild-type p53 following homeodomain-interacting protein kinase-2 knockdown. Cancer Res 2008; 68: 3707-3714.
78. Puca R, Nardinocchi L, Bossi G, et al. Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc. Exp Cell Res 2009; 315: 67-75.
79. Hainaut P, Milner J. A structural role for metal ions in the "wild-type" conformation of the tumor suppressor protein p53. Cancer Res 1993; 53: 1739-1742.
80. Meplan C, Mann K, Hainaut P. Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells. J Biol Chem 1999; 274: 31663-31670.
81. Srinivasan R, Roth JA, Maxwell SA. Sequence-specific interaction of a conformational domain of p53 with DNA. Cancer Res 1993; 53: 5361-5364.
82. Sun Y, Bian J, Wang Y, Jacobs C. Activation of p53 transcriptional activity by 1, 10-phenanthroline, a metal chelator and redox sensitive compound. Oncogene 1997; 14: 385-393.
83. Kundu JK, Surh YJ. Inflammation: Gearing the journey to cancer. Mutat Res 2008; 659: 15-30.
84. Moos PJ, Edes K, Fitzpatrick FA. Inactivation of wild-type p53 tumor suppressor by electrophilic prostaglandins. Proc Natl Acad Sci USA 2000; 97: 9215-9220.
85. 2 on proteasome. Biochemistry 2003; 42: 13960-13968.
86. 2 by nuclear factor-kappa B and other cellular proteins. Bioorg Med Chem Lett 2005; 15: 4057-4063.
87. 2 stabilizes, but functionally inactivates p53 by binding to the cysteine 277 residue. Oncogene 2010; 29: 2560-2576.
88. Biswal S, Maxwell T, Rangasamy T, Kehrer JP. Modulation of benzo[a]pyrene-induced p53 DNA activity by acrolein. Carcinogenesis 2003; 24: 1401-1406.
89. Furuhata A, Nakamura M, Osawa T, Uchida K. Thiolation of protein-bound carcinogenic aldehyde. An electrophilic acrolein-lysine adduct that covalently binds to thiols. J Biol Chem 2002; 277: 27919-27926.
90. Henry Y, Lepoivre M, Drapier JC, Ducrocq C, Boucher JL, Guissani A. EPR characterization of molecular targets for NO in mammalian cells and organelles. FASEB J 1993; 7: 1124-1134.
91. Surh YJ, Kundu JK, Li MH, Na HK, Cha YN. Role of Nrf2-mediated heme oxygenase-1 upregulation in adaptive survival response to nitrosative stress. Arch Pharm Res 2009; 32: 1163-1176.
92. Calmels S, Hainaut P, Ohshima H. Nitric oxide induces conformational and functional modifications of wild-type p53 tumor suppressor protein. Cancer Res 1997; 57: 3365-3369.
93. Chazotte-Aubert L, Hainaut P, Ohshima H. Nitric oxide nitrates tyrosine residues of tumor-suppressor p53 protein in MCF-7 cells. Biochem Biophys Res Commun 2000; 267: 609-613.
94. Yakovlev VA, Bayden AS, Graves PR, Kellogg GE, Mikkelsen RB. Nitration of the tumor suppressor protein, p53, at tyrosine 327 promotes p53 oligomerization and activation. Biochemistry 2010; 49: 5331-5339.
95. Cobbs CS, Whisenhunt TR, Wesemann DR, Harkins LE, Van Meir EG, Samanta M. Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cancer Res 2003; 63: 8670-8673.
96. Schonhoff CM, Daou MC, Jones SN, Schiffer CA, Ross AH. Nitric oxide-mediated inhibition of Hdm2-p53 binding. Biochemistry 2002; 41: 13570-13574.
97. Crow JP, Beckman JS, McCord JM. Sensitivity of the essential zinc-thiolate moiety of yeast alcohol dehydrogenase to hypochlorite and peroxynitrite. Biochemistry 1995; 34: 3544-3552.
98. Hainaut P, Mann K. Zinc binding and redox control of p53 structure and function. Antioxid Redox Signal 2001; 3: 611-623.
99. Hammond EM, Mandell DJ, Salim A, et al. Genome-wide analysis of p53 under hypoxic conditions. Mol Cell Biol 2006; 26: 3492-3504.
100. Koumenis C, Alarcon R, Hammond E, et al. Regulation of p53 by hypoxia: Dissociation of transcriptional repression and apoptosis from p53-dependent transactivation. Mol Cell Biol 2001; 21: 1297-1310.
101. Zhao Y, Chen XQ, Du JZ. Cellular adaptation to hypoxia and p53 transcription regulation. J Zhejiang Univ Sci B 2009; 10: 404-410.
102. Chandel NS, Vander Heiden MG, Thompson CB, Schumacker PT. Redox regulation of p53 during hypoxia. Oncogene 2000; 19: 3840-3848.
103. Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: Role of the HIF system. Nat Med 2003; 9: 677-684.
104. Bertout JA, Majmundar AJ, Gordan JD, et al. HIF2α inhibition promotes p53 pathway activity, tumor cell death, and radiation responses. Proc Natl Acad Sci USA 2009; 106: 14391-14396.
105. Hussain SP, Amstad P, He P, et al. p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. Cancer Res 2004; 64: 2350-2356.
106. Li Z, Shi K, Guan L, et al. ROS leads to MnSOD upregulation through ERK2 translocation and p53 activation in selenite-induced apoptosis of NB4 cells. FEBS Lett 2010; 584: 2291-2297.
107. Tan M, Li S, Swaroop M, Guan K, Oberley LW, Sun Y. Transcriptional activation of the human glutathione peroxidase promoter by p53. J Biol Chem 1999; 274: 12061-12066.
108. Meiller A, Alvarez S, Drane P, et al. p53-dependent stimulation of redox-related genes in the lymphoid organs of γ-irradiated-mice identification of Haeme-oxygenase 1 as a direct p53 target gene. Nucleic Acids Res 2007; 35: 6924-6934.
109. Liu XM, Chapman GB, Wang H, Durante W. Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in vascular smooth muscle cells. Circulation 2002; 105: 79-84.
110. Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W. Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 2002; 55: 396-405.
111. Behrend L, Mohr A, Dick T, Zwacka RM. Manganese superoxide dismutase induces p53-dependent senescence in colorectal cancer cells. Mol Cell Biol 2005; 25: 7758-7769.
112. Gong X, Kole L, Iskander K, Jaiswal AK. NRH:Quinone oxidoreductase 2 and NAD(P)H:Quinone oxidoreductase 1 protect tumor suppressor p53 against 20s proteasomal degradation leading to stabilization and activation of p53. Cancer Res 2007; 67: 5380-5388.
113. Asher G, Tsvetkov P, Kahana C, Shaul Y. A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73. Genes Dev 2005; 19: 316-321.
114. Asher G, Lotem J, Kama R, Sachs L, Shaul Y. NQO1 stabilizes p53 through a distinct pathway. Proc Natl Acad Sci USA 2002; 99: 3099-3104.
115. Asher G, Lotem J, Sachs L, Kahana C, Shaul Y. Mdm-2 and ubiquitin-independent p53 proteasomal degradation regulated by NQO1. Proc Natl Acad Sci USA 2002; 99: 13125-13130.
116. Anwar A, Dehn D, Siegel D, et al. Interaction of human NAD(P)H:Quinone oxidoreductase 1 (NQO1) with the tumor suppressor protein p53 in cells and cell-free systems. J Biol Chem 2003; 278: 10368-10373.
117. Gudkov AV. Converting p53 from a killer into a healer. Nat Med 2002; 8: 1196-1198.
118. Calabro-Jones PM, Fahey RC, Smoluk GD, Ward JF. Alkaline phosphatase promotes radioprotection and accumulation of WR-1065 in V79-171 cells incubated in medium containing WR-2721. Int J Radiat Biol Relat Stud Phys Chem Med 1985; 47: 23-27.
119. Pluquet O, North S, Richard MJ, Hainaut P. Activation of p53 by the cytoprotective aminothiol WR1065: DNA-damage-independent pathway and redox-dependent modulation of p53 DNA-binding activity. Biochem Pharmacol 2003; 65: 1129-1137.
120. Shen H, Chen ZJ, Zilfou JT, Hopper E, Murphy M, Tew KD. Binding of the aminothiol WR-1065 to transcription factors influences cellular response to anticancer drugs. J Pharmacol Exp Ther 2001; 297: 1067-1073.
121. Bykov VJ, Issaeva N, Shilov A, et al. Restoration of the tumor suppressor function to mutant p53 by a low-molecular-weight compound. Nat Med 2002; 8: 282-288.
122. Zache N, Lambert JM, Wiman KG, Bykov VJ. PRIMA-1MET inhibits growth of mouse tumors carrying mutant p53. Cell Oncol 2008; 30: 411-418.
123. Shi H, Lambert JM, Hautefeuille A, et al. In vitro and in vivo cytotoxic effects of PRIMA-1 on hepatocellular carcinoma cells expressing mutant p53ser249. Carcinogenesis 2008; 29: 1428-1434.
124. Bykov VJ, Lambert JM, Hainaut P, Wiman KG. Mutant p53 rescue and modulation of p53 redox state. Cell Cycle 2009; 8: 2509-2517.
125. Lambert JM, Gorzov P, Veprintsev DB, et al. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell 2009; 15: 376-388.
126. Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML. Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol 1998; 111: 656-661.
127. KIP1 and p53. Int J Oncol 2002; 21: 379-383.
128. Shankar S, Srivastava RK. Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol 2007; 30: 905-918.
129. Moos PJ, Edes K, Mullally JE, Fitzpatrick FA. Curcumin impairs tumor suppressor p53 function in colon cancer cells. Carcinogenesis 2004; 25: 1611-1617.
130. Bensaad K, Vousden KH. p53: New roles in metabolism. Trends Cell Biol 2007; 17: 286-291.
131. Lee MS, Yaar M, Eller MS, Runger TM, Gao Y, Gilchrest BA. Telomeric DNA induces p53-dependent reactive oxygen species and protects against oxidative damage. J Dermatol Sci 2009; 56: 154-162.
132. Ide T, Chu K, Aaronson SA, Lee SW. GAMT joins the p53 network: Branching into metabolism. Cell Cycle 2010; 9: 1706-1710.
133. Vousden KH. Alternative fuel - Another role for p53 in the regulation of metabolism. Proc Natl Acad Sci USA 2010; 107: 7117-7118.
134. Speidel D. Transcription-independent p53 apoptosis: An alternative route to death. Trends Cell Biol 2010; 20: 14-24.
135. Schetter AJ, Heegaard NH, Harris CC. Inflammation and cancer: Interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis 2010; 31: 37-49.
136. Legan M, Luzar B, Marolt VF, Cor A. Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions. World J Gastroenterol 2006; 12: 3425-3429.
137. Xu L, Li YM, Yu CH, et al. Expression of p53, p16 and COX-2 in pancreatic cancer with tissue microarray. Hepatobiliary Pancreat Dis Int 2006; 5: 138-142.
138. Kim KH, Park EJ, Seo YJ, et al. Immunohistochemical study of cyclooxygenase-2 and p53 expression in skin tumors. J Dermatol 2006; 33: 319-325.
139. Lim SC, Lee TB, Choi CH, Ryu SY, Kim KJ, Min YD. Expression of cyclooxygenase-2 and its relationship to p53 accumulation in colorectal cancers. Yonsei Med J 2007; 48: 495-501.
140. Jung H, Seong HA, Ha H. Critical role of cysteine residue 81 of macrophage migration inhibitory factor (MIF) in MIF-induced inhibition of p53 activity. J Biol Chem 2008; 283: 20383-20396.
141. Yang PM, Huang WC, Lin YC, et al. Loss of IKKβ activity increases p53 stability and p21 expression leading to cell cycle arrest and apoptosis. J Cell Mol Med 2010; 14: 687-698.
142. Appella E, Anderson CW. Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 2001; 268: 2764-2772.
143. Brooks CL, Gu W. Ubiquitination, phosphorylation and acetylation: The molecular basis for p53 regulation. Curr Opin Cell Biol 2003; 15: 164-171.
144. Kruse JP, Gu W. Modes of p53 regulation. Cell 2009; 137: 609-622.
145. Dongiovanni P, Fracanzani AL, Cairo G, et al. Iron-dependent regulation of MDM2 influences p53 activity and hepatic carcinogenesis. Am J Pathol 2010; 176: 1006-1017.
146. Hussain SP, Raja K, Amstad PA, et al. Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: Oxyradical overload diseases. Proc Natl Acad Sci USA 2000; 97: 12770-12775.